Abstract: A process for producing a collagen/hydroxyapatite (HA) composite scaffold comprises the steps of forming a homogenous suspension of collagen and HA in an acidic solution, lyophilising the suspension until a desired final freezing temperature is reached to produce the composite scaffold, and optionally cross-linking the composite scaffold, wherein the ratio of HA to collagen is at least 1:10 (w/w). Also provided is a collagen/hydroxyapatite (HA) composite scaffold comprising a homogenous distribution of hydroxyapatite within a porous, crosslinked, collagen matrix, wherein the ratio of HA to collagen is at least 1:10 (w/w). Suitably, the composite scaffold has a porosity of at least 99% (v/v), and a compressive stiffness of at least 0.3 KPa. Composite scaffolds of the invention may be used to provide osteoconductive bone implants and tissue engineering implants.

Abstract: A process for producing a collagen/hydroxyapatite (HA) composite scaffold comprises the steps of forming a homogenous suspension of collagen and HA in an acidic solution, lyophilizing the suspension until a desired final freezing temperature is reached to produce the composite scaffold, and optionally cross-linking the composite scaffold, wherein the ratio of HA to collagen is at least 1:10 (w/w). Also provided is a collagen/hydroxyapatite (HA) composite scaffold comprising a homogenous distribution of hydroxyapatite within a porous, crosslinked, collagen matrix, wherein the ratio of HA to collagen is at least 1:10 (w/w). Suitably, the composite scaffold has a porosity of at least 99% (v/v), and a compressive stiffness of at least 0.3 KPa. Composite scaffolds of the invention may be used to provide osteoconductive bone implants and tissue engineering implants.

Abstract: The invention relates to a method of screening a patient to identify and quantify risk of colorectal cancer, and thereby identify patients suitable for further invasive investigation such as a colonoscopy. The method employs auto-antibodies that are shown to correlate with colorectal cancer risk method and involves of assaying a biological sample from the individual for a combination of a plurality of biomarkers selected from SEQUENCE ID NO's: 1 to 12, where the combination of biomarkers is chosen such that detection of all biomarkers in the patient correlates to at least a 50% risk of the patient being positive for colorectal cancer. Detection of all of the combination of biomarkers indicates that the patient should undergo a colonoscopy. Kits for performing the method of the invention are also provided.

Abstract: A method of determining a suitable blood pressure lowering treatment for an individual comprises a step of assaying a biological sample from the individual for the presence or absence of the C-5312T SNP in a distal enhancer region of the renin gene. The presence of at least one T allele is indicative of an increased response to a blood pressure lowering treatment selected from the group comprising: angiotensin-2-receptor blockers; ACE Inhibitors; aldosterone receptor blockers; and beta-receptor blockers. The absence of at least one T allele is indicative of an increased response to a blood pressure lowering treatment selected from the group comprising: renin inhibitors; calcium channel blockers; and diuretics.

Abstract: Compounds comprising a metal complex having the structure [X—Y—Z-Mn+]p+.B are disclosed in which X is a histone deacetylase inhibitor, Mn+ is a DNA-binding heavy metal ion, Y is an aliphatic or aromatic spacer or is absent, and Z is a mono- or bi-dentate or chelating donor linker, or a bridging linker, P+ designates the charge on the complex ion, which may be positive, negative or absent and B is a counterion or is absent. The linker Z is labile and its metal complex X—Y—Z-Mn+ is capable of being hydrolysed in-vivo. The compounds find application in the treatment of cancer.

Abstract: A directly compressed orodispersible tablet comprises 0.1 to 50% of a ungranulated active agent (w/w), 10 to 80% of a sugar-based direct compression base, and 10 to 80% of a microcrystalline cellulose (MCC) direct compression base, and has a hardness of at least 60N, and a disintegration time of less than 40 seconds. The sugar-based direct compression base is a DC sugar alcohol, especially direct compression mannitol, and the MCC base is a silicified MCC, especially a Prosolv. The active is a hydrophobic active, typically a high-dose active. Also disclosed is a method of producing an orodispersible tablet comprising the steps of directly compressing a mixture of components at a compression force of at least 5 k N to form the tablet, wherein the mixture of components comprises 0.1 to 50% of an active agent (w/w), 10 to 80% of a sugar-based direct compression base (w/w); and 10 to 80% of a microcrystalline cellulose (MCC) direct compression base (w/w).

Abstract: The invention provides a method for preparing sulfur-containing compounds, the method comprising reacting a donor compound comprising at least one sulfur having at least one lone pair of electrons, with an acceptor compound; wherein the reaction occurs in the presence of an amine, optionally an amine catalyst, capable of activating the sulfur having at least one lone pair of electrons; and wherein the reaction occurs via the formation of an transient intermediate species, optionally a transient intermediate species, between the amine, optionally the amine catalyst and the donor compound; and wherein the donor compound is selected from the group consisting of a sulfurous acid, a sulfenic acid and a sulfinic acid or a salt, ester or amide of a sulfurous acid, a sulfenic acid and a sulfinic acid.

Abstract: The invention relates to a method for producing a multi-layer collagen scaffold. The method generally comprises the steps of: preparing a first suspension of collagen and freezing or lyophilising the suspension to provide a first layer; optionally preparing a further suspension of collagen and adding the further suspension onto the layer formed in the previous step to form a further layer, and freezing or lyophilising the layers, wherein when the layer formed in the previous step is formed by lyophilisation the lyophilised layer is re-hydrated prior to addition of the next layer; optionally, repeating the aforementioned step to form one or more further layers; and preparing a final suspension of collagen and pouring the final suspension onto the uppermost layer to form a final layer, and freeze-drying the layers to form the multilayer collagen composite scaffold.

Abstract: A method for the treatment or prevention of diarrhoea (or diarrhoeal disease) in an individual comprises a step of administering a therapeutically effective amount of a potent and or selective FXR agonist to the individual. A method for the treatment or prevention of dysregulated fluid transport into the intestine in an individual is also described, and comprises a step of administering a therapeutically effective amount of a potent and or selective FXR agonist to the individual.

Abstract: A method of producing microcapsules of the type having a core and a coating encapsulating the core comprises the steps of providing a core-forming fluid stream and a coating-forming fluid stream, providing a two spray nozzle arrangement having a core nozzle disposed concentrically about a second nozzle, spraying the core-forming fluid stream from the core nozzle and the coat-forming fluid stream from the concentric nozzle to produce microcapsules, and solidifying the microcapsules upon formation in a suitable gas. Spray drying or spray chilling may be employed as the means of solidifying the microcapsules. Microcapsules having a core and a solid coat are also described.

Abstract: The invention relates to the use of angiogenin, or a fragment or variant thereof, to treat diseases or conditions characterised by neuronal injury or death, or axonal degeneration, especially neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). The invention also describes a plurality of mutations of the human angiogenin gene which are associated with a neurodegenerative disease phenotype, and particularly a ALS phenotype. Also described is a method of assessing whether an individual is afflicted with, or generically predisposed to develop, a disease or condition characterised by neuronal injury or death, or axonal degeneration.

Abstract: A method of assessing recurrence status in a breast cancer patient comprises a step of assaying a biological sample from the patient for a level of a biomarker selected from S100? or HOX-C1I, wherein positive detection of one or both of the biomarkers is indicative of a positive recurrence status. Suitably, the method is a method of prognosis of poor disease free survival in a breast cancer patient, wherein positive detection of one or both of the biomarkers is indicative of poor disease survival. The method may also be a method of diagnosis of recurrence, wherein positive detection of circulating S100? is a diagnostic variable of recurrence. The method of diagnosis is carried out on a patient who is undergoing first line therapy and/or a patient who has had surgery to remove a primary breast tumour.

Abstract: The invention relates to a method of screening a patient to identify and quantify risk of colorectal cancer, and thereby identify patients suitable for further invasive investigation such as a colonoscopy. The method employs auto-antibodies that are shown to correlate with colorectal cancer risk method and involves of assaying a biological sample from the individual for a combination of a plurality of biomarkers selected from SEQUENCE ID NO's: 1 to 12, where the combination of biomarkers is chosen such that detection of all biomarkers in the patient correlates to at least a 50% risk of the patient being positive for colorectal cancer. Detection of all of the combination of biomarkers indicates that the patient should undergo a colonoscopy. Kits for performing the method of the invention are also provided.

Abstract: A method for controlling laser scanning microscopy of a probe comprising at least one cell is disclosed. The method comprises the steps of acquiring at least one initial image of the probe and identifying at least one cell within an initial probe image. Using a pre-defined grammar, a first set of scanning mode parameters for monitoring the cell(s); a first set of trigger parameters including at least one physiological parameter defining an event in the cell(s); and a second set of scanning mode parameters for monitoring at least one cell of the probe after an occurrence of the event is defined. A successive set of probe images acquired according to the first set of scanning mode parameters is provided and processed to determine if the event has occurred. Responsive to the event occurring, microscope modality is changed to the second set of scanning mode parameters.

Abstract: A process for producing a collagen/hydroxyapatite (HA) composite scaffold comprises the steps of forming a homogenous suspension of collagen and HA in an acidic solution, lyophilising the suspension until a desired final freezing temperature is reached to produce the composite scaffold, and optionally cross-linking the composite scaffold, wherein the ratio of HA to collagen is at least 1:10 (w/w). Also provided is a collagen/hydroxyapatite (HA) composite scaffold comprising a homogenous distribution of hydroxyapatite within a porous, crosslinked, collagen matrix, wherein the ratio of HA to collagen is at least 1:10 (w/w). Suitably, the composite scaffold has a porosity of at least 99% (v/v), and a compressive stiffness of at least 0.3 KPa. Composite scaffolds of the invention may be used to provide osteoconductive bone implants and tissue engineering implants.

Abstract: A method of generating a platelet reactivity profile of an individual comprises the steps of providing a platelet-containing biological sample from the individual, providing at least three platelet function modulators, each platelet function modulator being provided in at least three concentrations, and reacting an aliquot of the platelet containing sample with each concentration of each platelet function modulator in a separate reaction vessel. Platelet aggregation is then measured in each reaction vessel, and the platelet aggregation measurements are used to generate a dose response curve for each platelet function modulator, wherein the dose response curves obtained and/or one or more functions of the dose response curves obtained, comprise a platelet reactivity profile for the individual. Clinical applications of, and kits for carrying out, the methods of the invention are also described.

Abstract: A method of producing a fast-melt tablet comprises the steps of forming a mixture of components, the mixture comprising at least one fast dissolving sugar alcohol, at least one disintegrant or osmotic agent, and at least one an active component, blending the mixture for a period of time, and directly compressing the blended mixture at a compression force of typically between 5 and 2O kN to form the fast-melt tablet. The process of the invention does not involve any granulation step, thereby making the process more energy efficient and cost effective. The fast dissolving sugar alcohol is selected from the group comprising: mannitol; sorbitol; erythritol; xylitol; lactose; dextrose; and sucrose, and comprises at least 50%, preferably at least 60%, and more preferably at least 70%, of the tablet (w/w). The active component is suitably provided in the form of microparticles or microcapsules having an average diameter of less than 125 microns.

Abstract: The invention relates to the use of angiogenin, or a fragment or variant thereof, to treat diseases or conditions characterised by neuronal injury or death, or axonal degeneration, especially neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). The invention also describes a plurality of mutations of the human angiogenin gene which are associated with a neurodegenerative disease phenotype, and particularly a ALS phenotype. Also described is a method of assessing whether an individual is afflicted with, or generically predisposed to develop, a disease or condition characterised by neuronal injury or death, or axonal degeneration.

Abstract: A method of determining a suitable blood pressure lowering treatment for an individual comprises a step of assaying a biological sample from the individual for the presence or absence of the C-5312T SNP in a distal enhancer region of the renin gene. The presence of at least one T allele is indicative of an increased response to a blood pressure lowering treatment selected from the group comprising: angiotensin-2-receptor blockers; ACE Inhibitors; aldosterone receptor blockers; and beta-receptor blockers. The absence of at least one T allele is indicative of an increased response to a blood pressure lowering treatment selected from the group comprising: renin inhibitors; calcium channel blockers; and diuretics.

Abstract: A formulation of phenyloin suitable for topical application to a wound comprises a reservoir of phenyloin entrapped within a stabilising matrix, and an amount of dissolved phenyloin, wherein the dissolved phenyloin is in chemical equilibrium with the phenyloin entrapped within the stabilised matrix. The stabilised matrix may comprise a gel matrix, especially a gel matrix in which the polymer of the gel forms ion-pairs with the phenyloin. Also described are methods of treating a wound in diabetic and non-diabetic patients using a formulation according to the invention.